血管紧张素转换酶基因多态性与缺血性脑卒中后3个月认知的关系

目的探讨血管紧张素转换酶(ACE)基因插入/缺失(I/D)多态性与缺血性脑卒中后3个月非痴呆认知功能障碍(CIND)的关系。方法初发缺血性脑卒中患者185例,根据脑卒中后3个月认知功能测定将患者分为CIND组(42例)和对照组(143例)。PCR法测定ACE基因I/D多态性,采用简易智能状态量表和美国精神疾病统计和诊断手册第4版修订本进行认知测定。结果 CIND组与对照组ACE基因I/D多态性的基因型分布与Hardy-Weinberg平衡的理论频数之间差异无统计学意义。单因素分析发现,ACE基因DD基因型人群CIND发病风险是Ⅰ等位基因携带者的2.460倍(95% CI:1.084～5.582,P0.05)。多因素logistic回归分析发现,在共显性模式中,DD基因型人群CIND发病风险是Ⅱ基因型的3.185倍(95% CI:1.148～8.842,P0.05);在隐性遗传模式中,DD基因型人群CIND发病风险是Ⅰ等位基因携带者的2.852倍(95% CI:1.058～7.687,P0.05)。结论ACE DD基因型是缺血性脑卒中后CIND的独立危险因素,携带ACE DD基因型的患者可能更易发生CIND。     

A case control association study of ACE gene polymorphism (I/D) with hypertension in Punjabi population from Faisalabad,Pakistan

Angiotensin converting enzyme (ACE) is a key component of renin angiotensin aldosterone system. It converts angiotensin I to angiotensin II. Insertion/deletion (I/D) polymorphism of ACE gene is found associated with several complications. However, its association with hypertension and related metabolic diseases is still controversial. So, the aim of the present study was to check this association for Punjabi population from Faisalabad, Pakistan. For this purpose, blood samples (patients = 100, controls = 48) were collected and several biochemical parameters were measured. Genotyping for ACE (I/D) polymorphism was performed by polymerase chain reaction (PCR) assay.

ID genotype is found prevalent in the studied population as 41% in control subjects and 61% in patients. Furthermore, chi-square analysis showed significant (p = 0.005) difference for genotypic frequencies between both groups. One-way ANOVA for association of II, ID, and DD genotypes with anthropometric, clinical, and biochemical parameters showed that in patient group, DD genotype is significantly (p = 0.041) associated with systolic blood pressure (SBP). Moreover, ID genotype is found associated with the presence of cardiovascular diseases. This study concludes that DD genotype is strongly associated with higher SBP in hypertensive patients.     

Angiotensin-converting enzyme (ACE) gene II genotype protects against the development of diabetic peripheral neuropathy in type 2 diabetes mellitus

Background: Diabetic peripheral neuropathy (DPN) is one of the complications of type 2 diabetes mellitus (T2DM) that decreases the quality of life of T2DM patients. Very few studies have found an association between the development and progression of DPN in T2DM and angiotensin‐converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms. Methods: Using gene‐specific primers in a polymerase chain reaction, the presence of ACE I/D polymorphisms was screened for in 276 T2DM patients with DPN, 496 T2DM patients without DPN, and 331 control (non‐diabetic) subjects. Results: The distribution of the I/D genotypes was in Hardy–Weinberg equilibrium. The II genotype was significantly more prevalent in T2DM patients without DPN than the DD genotype (P < 0.05); however, there was no significant difference in the prevalence of the II and DD genotypes in T2DM patients with DPN (P = 0.78). Conclusion: The II genotype of the ACE gene has a protective effect against the development of DPN in T2DM patients. This suggests a role for the renin–angiotensin system in modulating neuropathy in T2DM.     

Angiotensin-Converting Enzyme Gene Polymorphism and Plasminogen Activator Inhibitor 1 Levels in Subjects with Cerebral Infarction

It has been suggested that the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is an independent risk factor for coronary artery disease, but its relation to cerebral infarction is still controversial. Plasminogen activator inhibitor 1 (PAI-1) is also a predictor of risk of atherothrombotic disease. In this study we investigated the association of the ACE gene polymorphism and plasma PAI-1 levels in subjects with cerebral infarction. We evaluated the genotype of the ACE gene in 26 subjects with and 28 subjects without a history of ischemic stroke. The ACE genotype was analyzed by the polymerase chain reaction. Plasma PAI-1 antigen levels were measured by ELISA. There were no differences in accepted risk factors between the groups with or without cerebral infarction. However, the frequency of the D allele was significantly higher in subjects with cerebral infarction (0.63) than in those without infarction (0.39) (² = 6.306, P = 0.012). The frequency of the DD genotype of the ACE gene was also significantly higher in subjects with than in those without cerebral infarction (DD: 46.2%, ID: 34.6%, II: 19.2% vs. DD: 14.3%, ID: 50.0%, II: 35.7%, ² = 6.689, P = 0.035). Plasma PAI-1 levels were not significantly different between groups with and without cerebral infarction. There was no association between the ACE genotype and PAI-1 levels. The DD genotype of the ACE gene is associated with cerebral infarction, which is independent of plasma PAI-1 level.     

The D/I Polymorphism in the Angiotensin-Converting Enzyme Gene and Chronic Obstructive Pulmonary Disease Risk: A Meta-Analysis

Abstract

Background: The deletion/insertion (D/I) polymorphism in the angiotensin-converting enzyme (ACE) gene has been implicated in susceptibility of chronic obstruction pulmonary disease (COPD), but a number of studies have reported inconclusive results. The aim of this study is to investigate the relationship between the D/I polymorphism in the ACE gene and COPD risk by meta-analysis. Method: We searched Pubmed database, Embase database, CNKI database and Wanfang database, covering all studies until October 10, 2011. Statistical analysis was performed by using the software Revman4.2 and STATA 10.0. Results: A total of 710 COPD cases and 862 controls in 10 case-control studies were included in this study. The results suggested that the DD homozygote carriers did not have an increased or decreased risk of COPD when compared with the heterozygote DI and II homozygote carriers. However, in the subgroup analysis by race, significant increased risks were found in Asian DD homozygote carriers (OR = 2.6 and 95% CI = 1.47–4.57 for DD vs. DI+II) but not in Caucasian DD homozygote carriers (OR = 0.91, 95%CI = 0.69–1.22, P = 0.54 for DD vs. DI+II). Conclusions: This meta-analysis suggested that the ACE gene is a COPD susceptible gene in Asian populations. Future studies are needed to validate our conclusions..     

ACE基因I／D多态性与缺血性脑卒中的关系

为了解血管紧张素转换酶（ACE）基因I／D多态性与中国人群缺血性脑卒中之间的关系,利用PCR和分子杂交技术对北京地区294例缺血性脑卒中患者及280例非卒中者的ACE基因I／D多态性进行了检测和分析。结果表明,I／D多态性在两组人群中的分布均符合Hardy-Weinberg遗传平衡定律,但该位点的基因型频率及等位基因频率在两组人群中分布无差异,与英国人群相比则有显著差异。提示ACE基因I／D多态性不是中国人群缺血性脑卒中发病的遗传学危险因素。     

老年脑卒中患者血浆ACE水平及其基因多态性的研究

血管紧张素转换酶(ACE)在肾素-血管紧张素-醛固酮系统(RASS)和激肽释放内原-激肽系统(KKS)中发挥着重要的作用。近年研究发现,ACE通过不同的遗传机制在心脑血管疾病的发生发展中发挥作用,其多态性决定了血浆和细胞内ACE浓度,是研究各类心脑血管疾病遗传易感性的候选基因,本文通     

Lack of association between the insertion/deletion polymorphism of the angiotensin-converting enzyme gene and vasospastic angina

Background and hypothesis: It has been suggested that the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is an independent risk factor for coronary atherosclerosis and myocardial infarction, but its relation to vasospastic angina has not been fully proven. In the present study, we investigated the possible relationship between the ACE I/D genotype and vasospastic angina. Methods: We explored the distribution of the ACE genotype in 20 patients with vasospastic angina without fixed coronary artery stenosis, 55 angina patients with fixed coronary artery stenosis, and 30 control subjects without coronary artery disease. Results: The frequency of the DD genotype in patients with vasospastic angina (DD: 30.0%, ID: 20.0%, II: 50.0%) did not differ from that in the control subjects (DD: 23.3%, ID: 26.7%, II: 50.0%), while the frequency in patients with coronary artery stenosis (DD: 43.7%, ID: 21.8%, II: 34.5%) was significantly higher than that in the control subjects. The frequency of the D allele also did not differ between patients with vasospastic angina (0.40) and control subjects (0.37), while the frequency was significantly higher in patients with coronary artery stenosis (0.55). Conclusions: These findings suggest that the ACE DD genotype is a potent genetic risk factor for organic coronary artery disease, while it confers no appreciable increase in risk of vasospastic angina. These results also suggest the diversity of the pathogenesis of vascular lesions in these two types of coronary artery disease.     

ACE I/D but not AGT (-6)A/G polymorphism is a risk factor for mortality in ARDS.

The intrapulmonary renin-angiotensin system via tissue concentration of angiotensin II or bradykinin may have multiple effects on pulmonary pathophysiology. Therefore, it was investigated whether the presence of the D allele of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism or the A allele of angiotensinogen (AGT) promoter polymorphism (-6)A/G are independent risk factors for 30-day survival in acute respiratory distress syndrome (ARDS) patients. In a prospective study, adults (Germans of Caucasian ethnicity) with ARDS (n = 84) were recruited from the current authors' intensive care unit and genotyped for the ACE I/D and the AGT (-6)A/G polymorphisms, as were 200 healthy Caucasian controls. Mortality was increased in the ACE DD genotype compared with the I allele, and the ACE I/D polymorphism was an independent prognostic factor for 30-day survival. Patients with a homozygous DD genotype were at highest risk for death (hazard ratio 5.7; 95% confidence interval 1.7-19.2) compared with the II genotype. In contrast, the AGT (-6)A/G polymorphism was neither associated with an increased risk for development of ARDS nor with outcome. In patients with acute respiratory distress syndrome, the angiotensin-converting enzyme insertion/deletion polymorphism but not the angiotensinogen (-6)A/G promoter polymorphism is an independent risk factor with a pronounced effect on 30-day survival.     

Association of genetic polymorphisms in the ace,apoe, and tgfβ genes with early onset ischemic heart disease

Background: The genetic factors that contribute to ischemic heart disease (IHD) are poorly understood, and it is likely that multiple genes acting independently or synergistically contribute to the risk of IHD and outcome. The genes for angiotensin-converting enzyme (ACE) and apolipoprotein E (ApoE) have been implicated independently in the risk of IHD. Hypothesis: This study examined whether genetic polymorphisms in the ACE and ApoE genes are associated with early onset IHD. Polymorphisms in a third gene, transforming growth factor β2 (TGF β2), with a known role in wound repair and cardiac development, are also examined with respect to early onset IHD. Methods: In all, 101 patients with IHD and onset of disease before 55 years for men and 60 years for women, and 100 controls with angiographically confirmed normal coronary arteries were recruited for this study. The ACE, ApoE, and TGF β2 genotypes were determined by polymerase chain reaction amplification or Southern blotting and were compared with the patient's clinical and family histories. Results and Conclusion: The frequency of the ACE D allele was significantly lower in the patient group (0.475) than in the control group (0.59, p = 0.03), which was attributed to a reduction in the number of patients with the DD genotype (patients: 24% DD, controls: 33% DD). Sudden cardiac death was also associated with the DD genotype. These data are consistent with the ACE D allele contributing to a fatal outcome. No association between the DD genotype and risk of myocardial infarction, presenting age, extent of vessel disease, family history, hypertension, or hypercholesterolemia was seen. Analysis of the ApoE genotype showed no association with early onset IHD. There was no evidence for a synergistic effect between the ACE and ApoE genotypes on the risk of early onset IHD. A polymorphism in the TGF (32 gene was rare and not associated with early onset IHD.     

血管紧张素转化酶基因插入/缺失多态性与冠心病发病的关系

目的 :探讨血管紧张素转化酶 (ACE)基因多态性与冠心病 (CHD)发病的关系。方法 :以人基因组DNA为模板 ,应用聚合酶链式反应 (PCR)检测 5 0例CHD组和 5 6例正常对照组ACE基因第 16内含子插入 /缺失 (I/D)多态性 ,并按性别分组计算各组基因型和等位基因频率。结果 :①在CHD组中 ,ACE基因DD基因型和D等位基因频率分别为 36 %和 6 0 % ,正常对照组分别为 16 %和 4 1% ,两者相比差异有统计学意义 (P <0 .0 1)。②男性CHD组DD基因型和D等位基因频率均显著高于对照组 (均P <0 .0 5 )。女性CHD组DD基因型频率显著高于对照组 (P <0 .0 1) ,D等位基因频率与对照组比较差异无统计学意义。结论 :CHD与ACE基因I/D多态性有显著相关性 ,不论男性和女性 ,ACE基因DD基因型均可能是CHD发生发展过程中重要的危险因素之一。     

血管紧张素转换酶基因多态性与老年脑卒中的相关性

目的探讨血管紧张素转换酶(ACE)基因多态性与老年脑卒中的相关性。方法选择186例脑卒中患者(脑卒中组)分为脑血栓组(126例)和脑出血组(60例),另选75例同期住院的非脑卒中患者作为对照组。采用PCR-RFLP技术,检测ACE第16内含子中长度为287bp碱基片段的插入/缺失情况,并分别测定其基因型频率和等位基因频率。结果脑卒中组D等位基因频率为41.9%,对照组为31.3%,两组比较差异有显著性意义(P<0.05);脑卒中组DD型基因频率为21.5%,对照组为9.3%,两组比较差异有显著性意义(P<0.05);脑血栓组和脑出血组D等位基因和DD型基因与对照组比较差异有显著性意义(P<0.05)。结论ACE基因多态性与老年人脑卒中相关,其DD型基因和D等位基因是老年脑卒中的危险因素。     

The ACE gene I/D polymorphism is not associated with the blood pressure and cardiovascular benefits of ACE inhibition

The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene might have consequences for the risks of vascular diseases. We examined the ACE genotype and the effects of a perindopril-based blood pressure-lowering regimen on macrovascular events, dementia, and cognitive decline among hypertensive and nonhypertensive patients with a history of cerebrovascular disease. ACE I/D genotypes were measured in 5688 of 6105 individuals with previous stroke or transient ischemic attack who participated in the PROGRESS trial. The DD genotype was significantly (P<0.0001) less frequent in Asian subjects (Chinese and Japanese, 14.7%) than in non-Asian subjects (32.0%). Controlling for racial background, there were no associations between ACE genotypes and cerebrovascular disease history or cardiovascular risk factors, including baseline blood pressure. The ACE genotype was not associated with the long-term risks of stroke, cardiac events, mortality, dementia, or cognitive decline; neither did the ACE genotype predict the blood pressure reduction associated with the use of the ACE inhibitor perindopril. Similarly, there was no evidence that the ACE genotype modified the relative benefits of ACE inhibitor-based therapy over placebo. This study provides no evidence that in patients with cerebrovascular disease, knowledge of ACE genotype is useful for predicting either the risk of disease or the benefits of perindopril-based blood pressure-lowering treatment.     

ACE基因I/D多态性与系统性红斑狼疮肾脏易感性关系的研究

研究血管紧张素转换酶基因Ｉ／Ｄ多态性与系统性红斑狼疮肾脏易感性的关系。方法用ＰＣＲ法和比色法分别测定５８例ＳＬＥ患者和４０例正常人的ＡＣＥ基因型和血清ＡＣＥ活性。结果确诊ＳＬＥ时临床有肾脏受累表现组ＡＣＥ基因ＤＤ型和Ｄ等位基因分布频率明显高于组，且ＤＤ型、ＤＩ型者血清ＡＣＥ活性前者明显于高于后者。     

Lower mortality in patients with the DD genotype of the angiotensin-converting enzyme gene after acute myocardial infarction.

OBJECTIVE: The angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been associated with different serum ACE concentrations and cardiac ACE activity. We assessed whether the ACE gene I/D polymorphism influenced cardiac mortality in Japanese patients with acute myocardial infarction. METHODS AND RESULTS: The ACE gene I/D polymorphism was determined in 441 consecutive patients with a first myocardial infarction.There were 69 patients (16%) with the DD genotype, 194 patients (44%) with the ID genotype, and 178 patients (40%) with the II genotype. During a mean follow-up of 9.4 months, there were 49 cardiac deaths (DD, n = 4; ID, n = 26; II, n = 19).The DD genotype was significantly associated with a lower mortality than the other genotypes (p = 0.0363) by Cox regression analysis adjusted for age, sex, site of myocardial infarction, Killip functional class, reperfusion therapy during acute phase, ACE inhibitor use, and beta-blocker use. CONCLUSIONS: In a selected cohort of Japanese patients, the DD genotype was associated with a significantly lower cardiac mortality after a first myocardial infarction.     

血管紧张素转化酶基因I/D多态性与卡托普利疗效和咳嗽不良反应的关系及其可能机制

目的 探讨血管紧张素转化酶基因I/D多态性与卡托普利降压效果、咳嗽不良反应发生率的关系及其可能机制.方法 筛选原发性高血压患者186例,检测血管紧张素转化酶基因I/D多态性,按血管紧张素转化酶I/D基因型分为II型、ID型和DD型三组,给予卡托普利降压(25 mg,2次/天),治疗8周,每周随访观察患者血压及咳嗽不良反应发生情况,失访20例.紫外法检测治疗前后血管紧张素转化酶水平、放射免疫法检测P物质水平.比较三组降压疗效、咳嗽不良反应发生率、血管紧张素转化酶及P物质水平的差异,并分析其可能的关系. 结果三组间治疗前后血压水平及下降幅度、治疗有效率及显效率差异均无显著性.共有68例患者出现咳嗽不良反应,II基因型组咳嗽不良反应的发生率为57.1%,显著高于ID基因型组和DD基因型组(P<0.05).三组间治疗前后血管紧张素转化酶水平差异显著 (P<0.001),在DD基因型组>ID基因型组>II基因型组(P<0.001).治疗前后P物质水平在II基因型、ID基因型和DD基因型组依次降低,但组间比较差异无显著性.P物质水平与血管紧张素转化酶水平存在显著负相关(r=-0.652, P<0.001).结论 卡托普利的降压疗效与血管紧张素转化酶基因I/D多态性无明显相关.携带血管紧张素转化酶II基因型的患者服用卡托普利后咳嗽不良反应的发生率较其它两型高.血管紧张素转化酶水平较低是高血压病患者出现血管紧张素转化酶抑制剂相关性咳嗽的重要原因,P物质是参与血管紧张素转化酶抑制剂相关性咳嗽不良反应发生的重要物质.     

血管紧张素转换酶基因多态性与不同性别慢性心力衰竭患者发病的相关性研究

目的探讨我国南方汉族人群中,血管紧张素转换酶(ACE)基因多态性与不同性别慢性心力衰竭(CHF)发病的关系。方法应用聚合酶链反应技术测定82例男性和48例女性CHF患者(试验组),以及89名男性和41名女性健康者(对照组)的ACE基因插入/缺失(I/D)多态性,并进行统计学比较。结果共检测出3种ACE基因型,分别为II型、ID型和DD型。试验组患者DD基因型及D等位基因均高于同性别对照组;与非DD型者相比,男性DD型者发生CHF的相对风险率为1.918;女性DD型者发生CHF的相对风险率为2.727。结论ACE基因I/D多态性与中国南方汉族人群不同性别CHF的发生均相关,D等位基因可能是该地区CHF发病的遗传危险因素。与男性相比,DD基因型女性罹患CHF的可能性更大。     

ACE基因插入/缺失多态与国人肺血栓栓塞症的关联研究

目的探讨血管紧张素转换酶(ACE)基因插入/缺失(ID)多态是否与肺血栓栓塞症存在关联,D等位基因是否增加国人肺血栓栓塞的危险。方法放射性核素肺通气-灌注扫描和(或)超高速CT检查并结合临床资料确诊的肺血栓栓塞症患者72例及性别、年龄匹配的健康对照者72名。调查静脉血栓形成和肺栓塞相关危险因素。酚-氯仿法提取基因组DNA,聚合酶链反应(PCR)鉴定ACE基因I/D多态点基因型。结果(1)病例组外伤、手术史及下肢静脉炎、静脉曲张发生率显著高于对照组,肺血栓栓塞家族史、心血管疾病家族史、口服避孕药、吸烟及饮酒史两组间差异无显著性。(2)健康对照组I、D等位基因频率分别为66％和34％,基因型分布符合Hardy-Weinberg平衡。Ⅱ、ID和DD基因型及I、D等位基因频率在病例和对照组差异无显著性。(3)进一步分别按显性、隐性和加性作用方式探讨ACE基因I/D多态与肺血栓栓塞症的关系,发现DD基因型个体肺栓塞危险显著增加(OR=2.51,P＜0.05),提示D等位基因为隐性作用方式。(4)将肺血栓栓塞患者按有无明确静脉血栓形成及肺栓塞环境诱因分组,结果显示无明确环境诱因组DD基因型频率显著高于对照组(27.1％vs14.3％;OR=2.64,P＜0.05),而有明确环境诱因组与对照组相比DD基因型频率差异无显著性。将肺血栓栓塞患者按是否合并下肢静脉血栓形成分组,结果显示肺栓塞合并下肢静脉血栓形成组DD基因型频率显著高于健康对照组(32.4％vs14.3％;OR=3.36,P＜0.05),单纯肺栓塞组与健康对照组比较差异无显著性。结论ACE基因I/D多态与国人肺血栓栓塞有关,D等位基因为隐性作用方式。DD基因型显著增加无明确静脉血栓形成及肺栓塞环境诱因个体肺栓塞危险;有下肢静脉血栓形成病史的DD基因型个体肺栓塞危险亦显著增加。     

Relationship between insertion/deletion (I/D) polymorphism of angiotensin converting enzyme (ACE) gene and susceptibility to type 2 diabetes mellitus in the Middle East and North Africa Region: A meta-analysis

Background and aimsThe association between insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and the risk of type 2 diabetes mellitus (T2DM) remains controversial. This study aimed to assess the effect of the ACE I/D gene polymorphism on T2DM in the Middle East and North Africa region (MENA region).Material and methodsOur data was extracted from PubMed, Science Direct, and the Web of Science. The predefined inclusion criteria included only the human case-control studies of English Peer-reviewed papers containing the data on genotype distributions of ACE I/D polymorphism and the T2DM risk. Review articles, meeting abstracts, editorials, animal studies, and studies not providing genotype distribution data or without sufficient data were excluded from this work. Results of this meta-analysis were expressed using odds ratios (OR) and 95% confidence intervals (CI). Indeed, the potential sources of heterogeneity and bias were examined by the Egger regression.ResultsOf 2755 identified articles, 10 studies were selected, including 2710 patients with T2DM and 2504 control subjects. Overall, we found a significant increased risk of T2DM susceptibility and the D allele of ACE I/D gene polymorphism (OR = 1.97; 95% CI = 1.33–2.93, p = 0.0007), recessive (OR = 2.16; 95% CI = 1.27–3.67; p = 0.004), dominant (OR = 2.45; 95% CI = 1.54–3.91; p = 0.0001), homozygote (OR = 3.35; 95% CI = 1.78–6.29; p = 0.0001) and heterozygote comparisons (OR = 1.76; 95% CI = 1.07–2.88; p = 0.024).ConclusionOur result suggests that this polymorphism may contribute to the development of T2DM in the MENA Region. This result needs to be confirmed by future well-designed studies with larger sample sizes in diverse populations and ethnicities.     

血管紧张素转换酶基因多态性与支气管哮喘易感性关系？…

目的 探讨血管紧张素转换酶（ＡＣＥ）基因插入与缺失多态性与支气管哮喘易感性、肺功能间的关系。方法 采用聚合酶链反应（ＰＣＲ）确定５０例哮喘患,７个哮喘家系所有个体以及５０名正常健康对照ＡＣＥ的基因型;乙酰甲胆碱激发试验测定气道的反应性;测定哮喘患肺的通气功能「一秒钟用力 呼气容积占预计值百分比（ＦＥＶ１占预计值％）,一秒钟用力气容积／用力肺活量（ＦＥＶ１／ＦＶＣ）」。结果 ＡＣＥ基因Ｄ纯合型